Sphingomyelinase, also known as sphingomyelin phosphodiesterase, is a type of phospholipase that breaks down the substrate sphingomyelin, which is a type of membrane lipid, into ceramide and phosphocholine. Sphingomyelinase is believed to play an important role in regulating the sphingomyelin metabolic pathway in vivo.
Sphingomyelinase is activated by extracellular cytokines, hormones, and the like. Ceramide thus produced is believed to play an important role as a lipid second messenger in various cellular functions, such as apoptosis, cell proliferation, differentiation, etc. This signal transduction pathway is referred to as the sphingomyelin pathway, and physiologically active substances known to be involved in this pathway are cell adhesion molecules such as tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), and like cytokines, Fas, D28, CD40-ligand, etc. These in vivo physiologically active substances are believed to be deeply involved in the onset of various diseases or the expression of various life phenomena, such as inflammation, cell death, immune system control, etc. This indicates the importance of the sphingomyelin pathway in vivo.
Sphingomyelinase-specific inhibitors are promising drugs for the prevention and treatment of cerebral hemorrhage, cerebral infarction, and like cerebrovascular diseases, head injuries, senile dementia represented by Parkinson's disease and Alzheimer's disease, and like neurodegenerative diseases, diabetes, obesity, arteriosclerosis, inflammatory diseases, immune diseases, cancer, renal diseases, and cardiac diseases. Thus, many sphingomyelinase inhibitors have been proposed (PTL 1 to 4).
However, no sphingomyelinase inhibitor has been developed that is effective for patients of senile dementia, the population of which is expected to increase in the future.